title: Telomere reprogramming and maintenance in porcine iPS cells.
abstract: Telomere reprogramming and silencing of exogenous genes have been demonstrated in mouse and human induced pluripotent stem cells (iPS cells). Pigs have the potential to provide xenotransplant for humans, and to model and test human diseases. We investigated the telomere length and maintenance in porcine iPS cells generated and cultured under various conditions. Telomere lengths vary among different porcine iPS cell lines, some with telomere elongation and maintenance, and others telomere shortening. Porcine iPS cells with sufficient telomere length maintenance show the ability to differentiate in vivo by teratoma formation test. IPS cells with short or dysfunctional telomeres exhibit reduced ability to form teratomas. Moreover, insufficient telomerase and incomplete telomere reprogramming and/or maintenance link to sustained activation of exogenous genes in porcine iPS cells. In contrast, porcine iPS cells with reduced expression of exogenous genes or partial exogene silencing exhibit insufficient activation of endogenous pluripotent genes and telomerase genes, accompanied by telomere shortening with increasing passages. Moreover, telomere doublets, telomere sister chromatid exchanges and t-circles that presumably are involved in telomere lengthening by recombination also are found in porcine iPS cells. These data suggest that both telomerase-dependent and telomerase-independent mechanisms are involved in telomere reprogramming during induction and passages of porcine iPS cells, but these are insufficient, resulting in increased telomere damage and shortening, and chromosomal instability. Active exogenes might compensate for insufficient activation of endogenous genes and incomplete telomere reprogramming and maintenance of porcine iPS cells. Further understanding of telomere reprogramming and maintenance may help improve the quality of porcine iPS cells.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Guangzhen
authors.initials: G
authors.lastname: Ji
authors.forename: Weimin
authors.initials: W
authors.lastname: Ruan
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Despoina
authors.initials: D
authors.lastname: Sakellariou
authors.forename: Jijun
authors.initials: J
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Maja
authors.initials: M
authors.lastname: Okuka
authors.forename: Jianyong
authors.initials: J
authors.lastname: Han
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.forename: Liangxue
authors.initials: L
authors.lastname: Lai
authors.forename: Sarantis
authors.initials: S
authors.lastname: Gagos
authors.forename: Lei
authors.initials: L
authors.lastname: Xiao
authors.forename: Hongkui
authors.initials: H
authors.lastname: Deng
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation / Q000502:physiology; D006652:Histological Techniques; D017404:In Situ Hybridization, Fluorescence; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D008856:Microscopy, Fluorescence; D060888:Real-Time Polymerase Chain Reaction; D013552:Swine; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000502:physiology* / Q000648:ultrastructure; D059505:Telomere Homeostasis / Q000502:physiology
chemical_list: D017931:DNA Primers; D019098:Telomerase